I. Field of the Invention
The present invention relates generally to the liquid chromatographic separation of components in a mixture. More particularly, the invention pertains to chiral zeolites as stationary phase for liquid chromatography columns, the preparation of this material, and methods of separating components, such as enantiomers, using this material.
II. Related Art
A molecule is chiral if it cannot be superimposed upon its mirror image and would exhibit optical activity. Enantiomers are examples of chiral compounds which have the same molecular formula and connectivity, but different orientation in three dimensional space. Their orientation in space is in such a way that they are the minor images of one another. A simple example would be right and left handed gloves. Such characteristics often influence their chemical interaction with the surrounding environment and may provide each with different types of interactions with proteins or other agents (Neue, 1997).
This differential behavior of enantiomers often becomes crucial in the synthesis and purification of pharmaceutical agents. A typical goal of pharmaceutical companies is to either make an agonist or antagonist for a cell surface receptor. For example, in the case of familial hypercholesterolemia disease, either the cholesterol receptors are defective in their structures or they are not synthesized at a normal rate. Both types of deficiencies result from an underlying genetic defect. The medication Lipitor® (atorvastatin), an R enantiomer, inhibits the enzyme that synthesizes cholesterol in the liver, causing a 25-45% drop in the serum cholesterol level. Side effects of such medication are usually nausea, vomiting, liver necrosis, muscle degeneration and fatigue. The main cause of such adverse effects is the presence of the S enantiomer, synthesized during manufacturing. The undesired enantiomer interacts differently at sites other than the cholesterol receptor site. Separation of the R and S enantiomers, therefore, is beneficial.
Pharmaceutical companies also use chirality as a tool to extend their patent lives of their blockbuster drugs. One example is the commercialization of the drug Nexium® by AstraZeneca. Nexium® is the S enantiomer of a racemic mixture previously sold as Prilosec®. The patent for Prilosec® expired in 2002 at which time the company then marketed the S enantiomer, Nexium®, to generate another decade of a blockbuster anti-ulcer drug sales (Stinson, 2007).
Another example of the importance of chirality lies in the purity analyses required by governmental agencies with respect to the manufacture and selling of pharmaceuticals. Regulatory authorities require thorough documentation regarding a drug substance, including chiral purity and stability. These requirements create a growing demand for rapid, precise and sensitive methods for analysis of enantiomeric purity (Peterson, 1997).
Liquid chromatography is a method commonly used to separate and purify components such as organic molecules and proteins. In this method, a stationary phase is subjected to mobile liquid phase in which a mixture of compounds is dissolved. In liquid chromatography that employs a column, the stationary phase is packed into the column and the liquid phase that carries the mixture to be analyzed passes through the column. Various properties of the components of the mixture, as well as the chosen stationary and mobile phases, may be exploited in order to best separate the components, such that the separate components elute from the column at different times. Unfortunately, enantiomers are often not easily separable by techniques that can separate other isomers or components due to their similar chemical structures.
There has never been a single liquid chromatography column capable of separating all enantiomeric mixtures. Thus, there is a perpetual demand for the development of new liquid chromatography columns for separation as more molecules are synthesized whose enantiomers exhibit different physiological characteristics.